Hemorrhagic fevers with significant mortality rates are associated with several rodent-borne arenaviruses. Of particular concern are the New World clade B arenaviruses, which include the causative agents of Argentine, Brazilian, Venezuelan and Bolivian hemorrhagic fevers. The viruses are normally transmitted by contact with rodents, but can also be transmitted person-to-person. No licensed vaccines are available in the US and only limited therapeutic effect from the non-specific antiviral drug ribavirin has been described. These properties, together with the likelihood that concentrated, weaponized forms would be highly infectious, mean that the viruses would pose a significant threat if developed as agents of biowarfare. [unreadable] [unreadable] Most of the available information about the arenaviruses have come from studies of the Old World arenavirus, LCMV. Relatively little is known about the New World viruses, and studies of the highly pathogenic clade B viruses are hampered by the need for BSL-4 containment laboratories. In order to address this problem, we have previously demonstrated that the surface glycoprotein of several arenaviruses can be incorporated into retroviral vector particles to generate functional surrogates of the arenavirus entry process. This includes the glycoprotein from Junin virus, the causative agent of Argentine hemorrhagic fever. Using these reagents, which can be worked with under BSL-2 conditions, we will undertake a comprehensive analysis of receptor usage and glycoprotein function within the clade B viruses. The knowledge gained from these studies will be used in the development of inhibitors directed against this important stage of the viral life-cycle. We believe that such approaches will provide a valuable complement to more conventional anti-viral strategies such as vaccine development. [unreadable] [unreadable]